This invention relates to salt forms and polymorphs of 5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide that are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to compositions including such salts, and to methods of using such compositions in the treatment of abnormal cell growth in mammals, especially humans.
The compound 5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, shown in structural formula 1, is a potent, selective oral inhibitor of receptor tyrosine kinases (RTKs) involved in
signaling cascades that trigger tumor growth, progression and survival. In vivo studies have shown that this compound has anti-tumor activity in diverse preclinical solid and hematopoietic cancer xenograft models. This compound, its preparation and use are further described in U.S. patent application publication No. US 2003/0092917, published May 15, 2003, the disclosure of which is incorporated herein by reference in its entirety.
In its free base form, 5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide is fairly crystalline, chemically and enantiomerically stable, and relatively non-hygroscopic. However, it would be advantageous to have salt forms having improved properties, such as improved crystallinity and/or decreased hygroscopicity, while maintaining chemical and enantiomeric stability properties.